Signs Of Primary Hyperparathyroidism Research Articles

Associative links between obesity and vitamin D levels as a risk factor for primary hyperparathyroidism

To date, the fact and mechanisms of associative links between vitamin D deficiency and primary hyperparathyroidism have been established. In turn, the level of 25 (OH) D is influenced by climatic conditions and the presence of obesity.
 Objective — to determine the supply of vitamin D in patients with endocrine disorders living in the climate in Ukraine, and to assess the impact of obesity on vitamin D levels and the development of hypercalcemia (signs of primary hyperparathyroidism).
 Materials and methods. Body mass index (BMI), serum levels of Ca and vitamin D were assessed in 145 patients, hospitalized in the clinic of Institute of Endocrine Pathology named after V. Ya. Danilevsky NAMS of Ukraine for various endocrine pathologies. The frequency of vitamin insufficiency and vitamin D efficiency, hypercalcemia was analyzed in groups with and without obesity.
 Results. The proportion of obese in the general group was 33.8 %, among men — 28.57 %, among women — 35.04 % (p < 0.05). The level of Ca in the blood was 2.39 ± 0.02 mmol/L, high Ca level occurred in 16.55 %, and obesity — in 49 (33.49 %) patients. Against the background of obesity, the level of Ca was 2.42 ± 0.02, and in non-obese people — 2.38 ± 0.02 (p > 0.05). Average level of vitamin D in the blood in the general group was 22.95 ± 0.73 mg/ml and was probably lower in the individuals with obesity (20.95 ± 1.39 vs. 24.09 ± 0.81 mg/ml in groups without obesity, p < 0.05). Distribution of the disease by the degree of vitamin D provision showed that in a cohort with low security vitamin D and the presence of obesity subgroup with a deficiency of vitamin D (20 — 29 ng/ ml) was 1.5 times bigger as the similar subgroup without obesity.
 Conclusions. In the climatic conditions of Ukraine, the average level of vitamin D in patients with endocrine pathology is within its deficiency (22.95 ± 0.73 ng/ ml). The presence of obesity in patients with endocrine pathology is associated with a probably lower supply of vitamin D, almost 1.5 times bigger the subgroup with vitamin deficiency (< 20 ng/ ml). The combination of obesity and vitamin D deficiency should be considered as a risk factor for primary hyperparathyroidism in patients with endocrine pathology. Such patients need regular monitoring of blood levels of calcium and parathyroid hormone, as well as medical support for adequate supply of vitamin D.

Primary hyperparathyroidism: Disease of diverse genetic, symptomatic, and biochemical phenotypes.

Genetic, symptomatic, and biochemical heterogeneity of patients with primary hyperparathyroidism (PHPT) has become apparent in recent years. An in-depth, evidence-based review of the phenotypes of PHPT was conducted. This review was intended to provide the resulting information to surgeons who operate on patients with hyperparathyroidism. This review revealed that the once relatively clear distinction between familial and sporadic PHPT has become more challenging by the finding of various germline mutations in patients with seemingly sporadic PHPT. On the one hand, the genetic and clinical characteristics of some syndromes in which PHPT is an important component are now better understood. On the other hand, knowledge is emerging about novel syndromes, such as the rare multiple endocrine neoplasia type IV (MEN4), in which PHPT occurs frequently. It also revealed that, currently, the classical array of symptoms of PHPT is seen rarely upon initial presentation for evaluation. More common are nonspecific, nonclassical symptoms and signs of PHPT. In areas of the world where serum calcium levels are checked routinely, most patients today are "asymptomatic" and they are diagnosed after an incidental finding of hypercalcemia; however, some of them have subclinical involvement of bones and kidneys, which is demonstrated on radiographs, ultrasound, and modern imaging techniques. Last, the review points out that there are three distinct biochemical phenotypes of PHPT. The classical phenotype in which calcium and parathyroid hormone levels are both elevated, and other disease presentations in which the serum levels of calcium or intact parathyroid hormone are normal. Today several, distinct phenotypes of the disease can be identified, and they have implications in the diagnostic evaluation and treatment of patients, as well as possible screening of relatives.

Peripheral Giant Cell Granuloma of the Jaws as First Sign of Primary Hyperparathyroidism: A Case Series.

Peripheral giant cell granulomas (PGCG) associated with hyperparathyroidism (HPT) are rare clinical entities. The aim of this study is to report on 21 PGCGs of the oral cavity as the first clinical sign of unknown primary HPT (PHPT) referred to the Complex Operating Unit of Odontostomatology of Aldo Moro University of Bari from 2009 to 2019. Surgical treatment consisted in conservative enucleation of the lesion, if possible, with contextual bone rim osteoplasty with piezosurgical tools and following histological examination. After histological diagnosis of PGCG, PHPT screening was performed dosing parathyroid hormone and serum calcium. In all the patients haematological investigation demonstrated elevated values of parathyroid hormone and serum calcium ruling out an unknown PHPT. Specifically, after endocrinological evaluation, patients showed PHPT related to: parathyroid adenoma (13), parathyroid hyperplasia (two, one of which occurred in a intra-thyroidal parathyroid), and parathyroid carcinoma (1) and were scheduled for surgical treatment. Considering that PGCGs could represent the first clinical sign of an undiagnosed PHPT and the screening of PHPT is a non-invasive and cheap exam, in case of histological diagnosis of a giant cell lesion, both central and peripheral, especially in patients with synchronous or history of methacronous giant cell lesions, parathyroidal screening should be mandatory.

Obstructive urolithiasis as first sign of primary hyperparathyroidism caused by a large parathyroid hyperplasia

Obstructive urolithiasis as first sign of primary hyperparathyroidism caused by a large parathyroid hyperplasia

Clinical manifestations of neurofibromatosis type 1 – a diagnostic and management challenge

Abstract Introduction. Neurofibromatosis type 1 (NF1), caused by mutation of the tumour-suppressor gene encoding neurofibromin, is an autosomal dominant disorder affecting various organs. Aim. The aim of the study was to discuss the clinical symptoms of NF1 based on seven cases of the disease with regard to the literature. Material and methods. We analyzed retrospectively patients with NF1 (4 females and 3 males) aged 19-52 who were treated at Endocrinology Department between 2003 and 2017. The diagnosis was made in childhood (4 patients) or in adolescence (3 cases), based on clinical symptoms and genetic tests. Results. Five patients had a positive family history of NF1, two cases represented spontaneous mutation. All of analyzed subjects presented café-au-lait spots and neurofibromas on the body. We observed neurological disorders such as: epilepsy (2 patients), Arnold-Chiari malformation (1 man), benign brain neoplasms (2 persons). Optic gliomas appeared in two cases. Tumours were also found in other organs, including the uterus (2 women), the lung, the adrenals, the pituitary and the parathyroid gland (with signs of primary hyperparathyroidism) – each tumour in another patient. Four subjects suffered from cognitive impairment. Skeletal manifestations of neurofibromatosis type 1 such as scoliosis (1 man) and short stature (6 patients) have been noted as well. Five patients presented thyroid disorders – hypothyroidism due to Hashimoto’s disease (4 patients), toxic nodular goiter (1 woman). Other clinical symptoms e.g. vitiligo, alopecia areata and coarctation of aorta have also been found. Conclusions. Variety of clinical symptoms causes that NF1 still remains a diagnostic and management challenge for many physicians. Therefore, multidisciplinary approach is needed to optimize patients’ treatment.

Large tumor of iliac bone in a young woman imitating malignant disease as a sign of primary hyperparathyroidism

Detection of a bone tumor in a young adult draws suspicion of neoplastic disease. A 22-year-old female was admitted for a bone tumor biopsy. MRI of the pelvis showed an osteolytic lesion at the level of the left sacroiliac joint. Radiologist suggested differential diagnosis between aneurysmal bone cyst and giant cell tumor of bone. Considering the high serum calcium and numerous foci of increased accumulation of the radioisotope on the bone scan, serum iPTH level was evaluated. The diagnosis of hyperparathyroidism was established. Neck ultra­sound revealed focal lesion corresponding to an enlarged parathyroid gland. Parathyroidectomy was performed. The iliac bone tumor showed to be a brown tumor of primary hyperparathyroidism, detected only rarely in adolescents. Non-specific symptoms and lack of routine control of serum calcium in youths make an early diagnosis difficult; moreover, pathological features of brown tumor and giant cell tumor of bone are very similar.

Osteitis fibrosa cystica\u2014a forgotten radiological feature of primary hyperparathyroidism

SummaryAlthough bone disease and stone disease are the universally accepted classical manifestations of primary hyperparathyroidism, clinical parathyroid bone disease is rarely seen today in the United States (<5% of patients) and Western Europe. Nevertheless, in a given patient, classical skeletal involvement can be the first sign of primary hyperparathyroidism, but not recognized because it is not usually included, anymore, in the differential diagnosis of this manifestation of skeletal disease. We describe four cases of primary hyperparathyroidism in which the first clinical manifestation of the disease was a pathological fracture that masqueraded as a malignancy. The presence of large osteolytic lesions gave rise to the initial diagnosis of a primary or metastatic cancer. In none of the reported cases was primary hyperparathyroidism with osteitis fibrosa considered as the diagnosis. It would seem to us that this course is best explained by the fact that in many countries such manifestations of primary hyperparathyroidism have become a rarity. In fact, the incidence of osteitis fibrosa among patients with primary hyperparathyroidism in the US is estimated as so rare, that in majority of medical centers routine x-ray examinations of the bones in these patients is not recommended. The X-ray or computed tomography scan findings of osteitis fibrosa cystica include lytic or multilobular cystic changes. Multiple bony lesions representing brown tumors may be misdiagnosed on computed tomography scan as metastatic carcinoma, bone cysts, osteosarcoma, and especially giant-cell tumor. Distinguishing between primary hyperparathyroidism and malignancy is made readily by the concomitant measurement of parathyroid hormone which in primary hyperparathyroidism, again, will be markedly elevated. In the hypercalcemias of malignancy, such elevations of parathyroid hormone are virtually never seen.ConclusionWhen radiographic evidence of a lytic lesion and hypercalcemia are present, primary hyperparathyroidism should always be considered in the differential diagnosis.

Intractable Localized Inguinal Pruritus as a Sign of Primary Hyperparathyroidism

Intractable Localized Inguinal Pruritus as a Sign of Primary Hyperparathyroidism

Brown tumor of the palate as first manifestation of primary hyperparathyroidism: a case report

Brown tumor is one of the lesions that develop in patients with hyperparathyroidism. Skeletal bones including maxillo-facial ones can be the site of this lesion. Owing to the improve methods of blood analysis most of cases of primary hyperparathyroidism are diagnosed early and asymptomatically making advanced disease with bone lesions extremely rare. This article contains a case of a 43-year-old female patient who presented with palatal swelling as the first sign of primary hyperparathyroidism. The diagnosis was suggested by the histological findings and confirmed by the endocrinologic status.

Codon Y791F Mutations in a Large Kindred: Is Prophylactic Thyroidectomy Always Indicated?

RET proto-oncogene mutations are associated with medullary thyroid carcinomas usually requiring preventive thyroidectomy in gene carriers. We present a large kindred with the Y791F mutation in the RET proto-oncogene that did not have medullary thyroid carcinomas. Eight members of a Danish family with the Y791F mutation participated. All gene carriers underwent pentagastrin testing, and measurements of serum calcitonin. In the index person, exons 10, 11, and 13-16 of the RET proto-oncogene were screened. In the rest of the individuals only exon 13 was analysed. Mutation analysis was done by direct bidirectional sequencing of PCR products on an ABI 3100 Genetic Analyzer (Applied Biosystems, Foster City, CA, USA). The index person was screened genetically due to goitre at a young age. A total of 27 members of the family underwent genetic testing. Twelve (44.4%, 95% CI: 25.5%-64.7%) had the mutation (age range 13-84 years). None of these had abnormal pentagastrin tests (0%, 95% CI: 0%-26.5%). We found no significant differences in basal serum calcitonin concentrations between gene carriers (mean +/- SD: 0.16 +/- 0.54 pmol/l, n = 11) and non-gene carriers (0.55 +/- 0.86 pmol/l, n = 6, 2 P = 0.29). None showed signs of primary hyperparathyroidism or phaeochromocytoma. The Y791F RET proto-oncogene mutation may have a low penetrance. In selected cases, prophylactic thyroidectomy may be replaced by watchful waiting with repeated pentagastrin testing, provided careful evaluation of risks and benefits is performed.

How asymptomatic is asymptomatic primary hyperparathyroidism?

We observed several cases of patients who believed they were free of symptoms or signs of primary hyperparathyroidism (pHPT) preoperatively. reported a change of complaints following parathyroidectomy (PTX). We, therefore, decided to examine a larger group of patients to discover if these findings were incidental or of more general significance. The role of PTX in these patients with asymptomatic pHPT remains controversial. In 1991 criteria were defined at a NIH-consensus conference, according to which patients qualify for either operative therapy or long term medical surveillance. Until now, it was generally believed that the majority of asymptomatic patients would never develop symptoms. In a epidemiological cohort-study, the perioperative data of 582 consecutive patients with pHPT, including 116 asymptomatic patients (20.9%), who underwent parathyroidectomy between 1987 and 1998 were evaluated by uni- and multivariate analysis. At a median of 72 months postoperatively, all patients underwent a planned follow-up which included a standardised, validated questionnaire, physical examination and laboratory investigations. Eighty-six patients who were asymptomatic preoperatively were available for follow-up. Only eight (9.3%) were definitely asymptomatic, 4.6% of the entire, representative cohort. Postoperative improvement was reported in 81.4% of the "asymptomatic" patients. Multivariate analysis did not reveal a single or a set of preoperative measurements, that would allow to predict the retrospectively definitely asymptomatic patient. PTX resulted in normocalcaemia in 98.8% of preoperatively asymptomatic patients, with an operative morbidity of 1.2% and no mortality. Many apparently asymptomatic patients with pHPT will only realise that they did in fact have preoperative symptoms in retrospect, following PTX. This study suggests that using an up-to-date definition of asymptomatic pHPT, there are only a small number of truly asymptomatic patients and that these cannot be predicted preoperatively, as their symptoms may become apparent only after PTX. "Asymptomatic" patients with pHPT may share the same objective and subjective benefits from PTX as symptomatic patients. They should be operated as soon as the diagnosis is established.

Hypocalcaemic primary hyperparathyroidism.

A patient with many symptoms and signs of primary hyperparathyroidism had hypocalcaemia when first seen. Bone section histology showed osteomalacia and osteitis fibrosa, and the hyperparathyroidism at this stage was considered to be secondary to osteomalacia with postgastrectomy steatorrhoea. On treatment with vitamin D (with disappearance of her bone pains and weakness) she developed hypercalcaemia. She regained her health after removal of a 6-g. parathyroid adenoma. Normal histology was shown in another parathyroid gland.We believe that the initial hypocalcaemia was due to vitamin-D deficiency, which produced ineffective hyperparathyroidism until it was corrected. A review of the few reports of patients with autonomous hyperparathyroidism with steatorrhoea and osteomalacia does not support the argument that these patients had "tertiary" disease. It suggests that most of them, like our patient, had primary hyperparathyroidism.

Dental aspects of hyperparathyroidism

This report is based upon the study of thirteen dentulous patients with histologically proved hyperparathyroidism. The patients are in addition to the forty-two consecutive dentulous patients with surgically proved hyperparathyroidism previously reported. Four of the total of fifty-five patients in both studies revealed dental-structure changes of loss of lamina dura, giant-cell tumors, and demineralization. Involvement of the jawbones appears to be a late change and the least sensitive indicator of parathyroid overactivity, as compared to hypercalcemia, renal phosphate leak, hypophosphatemia, elevated alkaline phosphatase levels, and other bony lesions. It is concluded that the loss of lamina dura and the apearance of giant-cell tumors are late signs of hyperparathyroid bone disease, which is itself a late complication of primary hyperparathyroidism. However, even though infrequently found, changes in the dental structures may be the first sign of primary hyperparathyroidism. Roentgenographic jawbone alterations must be differentiated from other diseases which may have the same roentgenographic manifestations. Giant-cell lesions may reflect local neoplasia, an inflammatory process, or a parathyroid adenoma. Therefore, correlation of microscopic, clinical, roentgenographic, and laboratory findings is necessary before one can arrive at a definitive diagnosis.